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3. BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling

Author

Grishina, Irina B., Kim, Sung Yup, Ferrara, Christopher, Makarenkova, Helen P., and Walden, Paul D.

Subjects
Questions and answers -- Analysis, Stem cells -- Analysis, Bone morphogenetic proteins -- Analysis, Hormones, Sex -- Analysis, Fibroblast growth factors -- Analysis, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.08.018 Byline: Irina B. Grishina (a), Sung Yup Kim (a), Christopher Ferrara (a), Helen P. Makarenkova (b), Paul D. Walden (a) Keywords: BMP7; pSmad1; Notch1; Hes1; Prostate; Branching morphogenesis; Urogenital sinus; Epithelium; Mesenchyme Abstract: The mouse prostate gland develops by branching morphogenesis from the urogenital epithelium and mesenchyme. Androgens and developmental factors, including FGF10 and SHH, promote prostate growth (Berman, D.M., Desai, N., Wang, X., Karhadkar, S.S., Reynon, M., Abate-Shen, C., Beachy, P.A., Shen, M.M., 2004. Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev. Biol. 267, 387-398; Donjacour, A.A., Thomson, A.A., Cunha, G.R., 2003. FGF-10 plays an essential role in the growth of the fetal prostate. Dev. Biol. 261, 39-54), while BMP4 signaling from the mesenchyme has been shown to suppresses prostate branching (Lamm, M.L., Podlasek, C.A., Barnett, D.H., Lee, J., Clemens, J.Q., Hebner, C.M., Bushman, W., 2001. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev. Biol. 232, 301-314). Here, we show that Bone Morphogenetic Protein 7 (BMP7) restricts branching of the prostate epithelium. BMP7 is expressed in the periurethral urogenital mesenchyme prior to formation of the prostate buds and, subsequently, in the prostate epithelium. We show that BMP7.sup.lacZ/lacZ null prostates show a two-fold increase in prostate branching, while recombinant BMP7 inhibits prostate morphogenesis in organ culture in a concentration-dependent manner. We further explore the mechanisms by which the developmental signals may be interpreted in the urogenital epithelium to regulate branching morphogenesis. We show that Notch1 activity is associated with the formation of the prostate buds, and that Notch1 signaling is derepressed in BMP7 null urogenital epithelium. Based on our studies, we propose a model that BMP7 inhibits branching morphogenesis in the prostate and limits the number of domains with high Notch1/Hes1 activity. Author Affiliation: (a) Department of Urology, New York University School of Medicine, VAMC, 423 East 23rd Street, 18064-South, New York, NY 10010, USA (b) The Neuroscience Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA Article History: Received 10 June 2004; Revised 11 August 2005; Accepted 11 August 2005

Published
2005

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